We and others have observed that oxidants are formed during inflammatory tissue injury and are known to be generated through stimulation of leukocytes. In order to evaluate the role of oxidants in the pathogenicity of inflammatory disease, it will be essential to define the cellular and molecular targets of oxidants. The applicant proposes to study the effect of specific oxidants on molecular targets of cells. In particular, the proposed studies are aimed at: 1.0 Definition of cellular targets of H202 1.1 Definition of cellular targets of HOCl and chloramines 1.2 Determination of the effects of oxidants derived from stimulated PMNs on target cells with special emphasis on damage of DNA. Once specific targets of oxidants are defined on a molecular level, it will be possible to determine oxidant involvement in inflammatory disease by looking for the formation of these "footprints" in vivo.